Background: Ontario and other Canadian provinces fund multi-gene sequencing panels as the initial testing approach for patients with epilepsy. However, genetic testing guidelines issued by the US-based National Society for Genetic Counselors and endorsed by the American Epilepsy Society recommend exome as a first-line test. We explored the theoretical improvements in diagnostic yield when selecting exome over provincially-funded panels (PFPs). Methods: Our comparative analysis used a list of 768 diagnostic genes and 4474 diagnostic variants identified in diagnostic exome cases involving clinical indications of seizure. We compared these lists to the genes included in two PFPs (190 genes and 474 genes) to see which exome-identified genes and variants would have been captured by the PFPs. Results: Most exome-identified diagnostic genes may have been missed by the PFPs (82% and 65% for the 190 and 474-gene PFPs), and close to half of the exome-identified diagnostic variants (62% and 43% for the 190 and 474-gene PFPs) may have been missed. Conclusions: Exome-based testing captures a broader range of diagnostic genes and more diagnostic variants than PFPs. The adoption of exome over panels as a first-line test may lead to improved diagnostic rates and permit earlier treatment for individuals with seizures.